Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration
Abstract
:1. Introduction
2. Nanostructured Materials for Enhanced Bone Regeneration
Nanoparticles Classifications
3. PLGA Nanoparticles and Their Properties
3.1. Modulating PLGA Properties for Enhanced Bone Regeneration
3.1.1. PLGA Physicochemical Properties
3.1.2. Biodegradation
3.1.3. Mechanical Strength
3.1.4. Particle Size and Morphology
3.2. Surface Modifications
3.2.1. PEGylation
3.2.2. Surfactants
3.2.3. Phospholipids
3.2.4. Surface Ligands
4. PLGA Nanoparticles: Therapeutic Uses
5. Techniques for PLGA-Based Nanostructure Preparation
5.1. The Emulsion–Solvent Evaporation Method
5.2. Nanoprecipitation Method
5.3. Electrospinning Method
5.4. 3D Printing Method
5.5. Other Methods
6. Fabrication Forms of PLGA Particles
6.1. PLGA as Nano- or Microparticles
6.2. PLGA Scaffolds
7. PLGA-Loaded Bioactive Molecules for Bone Regeneration
7.1. Peptides
7.1.1. BMP-2
7.1.2. Other Proteins
7.2. Drugs
7.3. Ions
8. Cytotoxicity and Safety Evaluation of PLGA Nanoparticles
9. Commercial Products Based on PLGA
Product Name | Composition | Clinical Usage | Advantages | Disadvantages | References |
---|---|---|---|---|---|
Polyglactin 910 (Vicryl suture) | Copolymer of glycolide and lactide | Internal suture | Low friction, easy to handle, and fast absorption | Can cause inflammation if it remains in the skin for more than 7 days, causing scar tissue or stitched sinuses | [202,208] |
Coated Vicryl Plus | Copolymer of glycolide and lactide coated with an antibiotic agent | Surgical incision suture | Prevent bacterial infection at the surgical site | Low efficacy in oral, breast, and cardiac surgeries | [202,209] |
OsteoScafTM scaffold | PLGA and calcium phosphate | Clot-retention device and osteoconductive support for bone growth | Preserve the alveolar bone structure following tooth extraction | low mechanical properties and local acidification of PLGA can lead to clinical failure | [203,210] |
Biosteon interference screw | HA particles within a PLLA matrix | Reconstruction of anterior cruciate ligaments and suture anchors for rotator cuff repairs | Osteoconductive material and HA particles improve strength retention, bone-bonding potential, and pH buffering during graft healing | Differences in the resorption rates between PLGA and HA particles could induce potential complications | [204,211] |
Bilok interference screws | β-TCP particles within a PLLA matrix | Ligament restoration and suture anchors in rotator cuff repairs | Enhances structural integrity, faster degradation, and increased hydrophilicity | Screw can fracture during insertion or after insertion | [205,212] |
ActivaScrewTM Interference screw | Proprietary blend of PLGA | Fixation of tissue, including a ligament, tendon to bone, or bone–tendon to bone | Easy guided insertion and high strength; after operation, screw dimensions slightly change, improving the screw’s fit and isoelasticity | - Cannot be used in early weight-bearing rehabilitation due to their elasticity - Additional casting is required to maintain reduction and alignment | [206,213] |
Milagro Advance Interference Screw | 70% PLGA and 30% β-TCP | Attachment of soft tissue grafts or bone-tendon-bone grafts to the tibia and/or femur during the cruciate ligament reconstruction procedure. | Rapid insertion, excellent fixation strength, and enhanced bone engagement | Marrow edema around bone tunnels was seen 3 months after the operation and reduced after 6 months | [214,215] |
Biosure Regenesorb Interference Screw | β-TCP/PLGA/ calcium sulfate | Fixing ligaments, tendons, soft tissues, or bone-tendon-bone grafts in knee surgery | Open architecture allows bone ingrowth through the screw and attachment to the graft, increasing strength | Require a special surgical fixation technique | [207,216] |
10. Current Challenges and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Classifications | Advantages | Disadvantages | References |
---|---|---|---|
Organic nanoparticles:
| Hydrophilic, non-toxic, biodegradable, easy synthesis process, well-defined structure, changeable size, good surface characteristics, controlled drug delivery. | Sensitive to thermal and electromagnetic radiation such as heat and light, they are more susceptible to change in nature, leading to their elimination from the body. | [23,24,25] |
Inorganic nanoparticles:
|
| Long-term toxicity, genotoxicity, and oxidation vulnerability may induce an inflammatory response. | [26,27] |
Carbon-based nanoparticles:
| Electrical conductivity, heat conductivity, good mechanical properties, high stability, high surface area, excellent optical activity. |
| [28,29] |
Intended Use | Active Agent | Targeted Delivery | PLGA Formulation | In-Vitro/ In-Vivo | Results | References |
---|---|---|---|---|---|---|
Anticancer | DOX | Use of FA for targeted delivery against folate receptors | PLGA/DOX/ γPGA/FA NPs | HeLa cells | PLGA/DOX/γPGA/FA NPs have targeted and pH-dependent release. | [101] |
DOX | Thermogel | DOX-loaded-liposome fabricated within PLGA-PEG-PLGA thermogel | 4T1 cells (in vivo) BALB/c mice | The thermogel proved to have no burst, controlled DOX release in vitro, and enhanced anticancer activity in vitro and in vivo with fewer side effects. | [102] | |
DOX | Anti-EGFR antibody cetuximab (C) Light-induced chemotherapy (NIR) | DOX/PLGA/PD/ PEG/C core-shell NPs | UMSCC 22A cells | The core-shell NPs with photothermal activity and targeting antibodies have enhanced and safer chemotherapeutic activity. | [103] | |
DOX pEGFP DNA solution | FA | Polymeric-liposome-loaded-DOX/PLGA nanosphere complexed with pEGFP DNA | MDA-MB-231 cells | The core-shell nanospheres succeeded in co-delivery of DOX and pEGFP DNA into breast cancer cells. | [104] | |
DOX | CPPs-LMWP [C24LMWP] | DOX/PLGA/C24-LMWP NP | A549/T, MCF-7/ADR, and 293T | LMWP delivered DOX/PLGA NPs by targeting MDR cancer cells overexpressing heparan sulfate proteoglycans. | [105] | |
DOX (Adriamycin) | DOX/PLGA microspheres loaded HA/collagen scaffold (DOX/PLGA/HAC) | BMSC collected from the bone marrow of femurs of male Wistar rats (in vivo) | DOX/PLGA/HAC scaffolds exhibited bone repair activity with no obvious inflammatory signs, as well as enhanced antineoplastic activity. | [106] | ||
Diacetate acetyl curcumin (AC) | AC/PLGA/liposome | HeLa and HDFa cells | A new drug delivery system with theranostic applications. | [107] | ||
Mitoxantrone (MXT) | Ultrasound-responsive liposome | MXT/PLGA /Lip | Sustained release of NPs with ultrasound-responsive activity. | [108] | ||
Recombinant methioninase (rMETase) | Single-chain variable fragment (scFV) antibody | scFV/rMETase/PLGA/Lip | SGC-7901 cells | scFV/PLGA/Lip NPs have higher cellular uptake in gastric cancer cells. scFV/rMETase/PLGA/Lip enhanced the anticancer activity of rMETase. | [109] | |
Cisplatin | Anti-VEGF antibody Avastin® | Avatin®/Lip/ PLGA/Cis | SiHa cells | PLGA forms stable Cis NPs with sustained release. Encapsulating the NP into Avastin®-conjugated liposomes enhances its intracellular uptake and thus its anticancer activity. | [110] | |
Luteolin (L) | Antibody (PD-L1) | L/PD-L1/ PLGA/Lip | HepG2 cells | NPs with improved in vitro release profiles, cancer cellular uptake, and migration inhibition. | [111] | |
Paclitaxel and elacridar (ELC) | Transferrin (Tf) | Tf/PTX-ELC /PLGA NPs | EMT6/AR1.0 cells | Co-delivery of PTX and P-gp inhibitors to overcome multidrug resistance and maintain intracellular therapeutic drug levels. | [112] | |
Antioxidant | Resveratrol | PLGA-oil nanohybrids (PONHs)/resveratrol | Normal monkey kidney (Vero) cells | PONH decreased cytotoxicity and improved the scavenging activity of resveratrol in vitro. | [113] | |
Gallic acid (GA) | GA/PLGA | S. aureus HaCaT cells | GA/PLGA NPs with controlled release in vitro, excellent antioxidant activity, good antimicrobial activity against S. aureus, and good biocompatibility. | [114] | ||
Rutin (vitamin P) and NAAA inhibitor (URB894) | rutin/URB894/PLGA NPs | C-28 and NCTC-2544 cells | The co-encapsulation of rutin and URB894 in PLGA NPs resulted in synergistic antioxidant activity. | [115] | ||
Antibiotic | Clindamycin | Clindamycin/ PLGA NPs | Formation of sustained clindamycin release up to 3 months. | [116] | ||
Gentamicin (gentAOT) | Zirconia scaffolds | gent AOT/ PLGA NPs | S. aureus osteoblast-like MG-63 cells | gent AOT/PLGA NPs adequately inhibited the growth of S. aureus. | [117] | |
Anti-atherosclerosis | Simvastatin (SIM) | SIM/PLGA/Lip | RAW 264.7 cells (in vivo) atherosclerotic model rabbits | SIM/PLGA/Lip NPs showed increased circulation time and enhanced athero-protective activity. | [118] | |
Anti-restenosis | Dexamethasone (DEX) or Rapamycin (Rap) | PEO-PLGA/DEX PEO-PLGA/Rap NPs were then coated with gelatin | In vitro-controlled release of coated NPs. | [119] |
Method | Advantage | Disadvantage | References |
Emulsion–solvent evaporation | Simple, spherical particles | Polydisperse particle sizes and high sheer forces degrade the active agent | [136,137,138] |
Nanoprecipitation | High yield and reproducibility, and high encapsulation efficiency of hydrophobic drugs | Polydisperse particle sizes and high sheer forces degrade the active agent | [114,115,118,139] |
Electrospinning | Easily forms uniformly fibrous, and multilayered scaffolds | Need electrospinning equipment and 2D nanofibrous membranes | [117,135,140] |
3D printing | Adjustable sizes and shapes of the fabricated and monodispersed scaffolds | 3D printer is required; it is not compatible with all types of polymers, and drugs may degrade during the drying step | [141,142,143] |
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Hassan, M.; Abdelnabi, H.A.; Mohsin, S. Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration. Pharmaceutics 2024, 16, 273. https://doi.org/10.3390/pharmaceutics16020273
Hassan M, Abdelnabi HA, Mohsin S. Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration. Pharmaceutics. 2024; 16(2):273. https://doi.org/10.3390/pharmaceutics16020273
Chicago/Turabian StyleHassan, Mozan, Hiba Atiyah Abdelnabi, and Sahar Mohsin. 2024. "Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration" Pharmaceutics 16, no. 2: 273. https://doi.org/10.3390/pharmaceutics16020273